Lambert Wendi S, Carlson Brian J, van der Ende Alice E, Shih Grace, Dobish Julia N, Calkins David J, Harth Eva
The Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Chemistry, Vanderbilt University, Nashville, TN, USA.
Transl Vis Sci Technol. 2015 Jan 13;4(1):1. doi: 10.1167/tvst.4.1.1. eCollection 2015 Jan.
We examined the efficacy of an extended-release drug delivery system, nanosponge (NS) encapsulated compounds, administered intravitreally to lower intraocular pressure (IOP) in mice.
Bilateral ocular hypertension was induced in mice by injecting microbeads into the anterior chamber. Hypertensive mice received NS loaded with ocular hypotensive drugs via intravitreal injection and IOP was monitored. Retinal deposition and retinal ganglion cell (RGC) uptake of Neuro-DiO were examined following intravitreal injection of Neuro-DiO-NS using confocal microscopy.
Brimonidine-loaded NS lowered IOP 12% to 30% for up to 6 days ( < 0.02), whereas travoprost-NS lowered IOP 19% to 29% for up to 4 days ( < 0.02) compared to saline injection. Three bimatoprost NS were tested: a 400-nm NS and two 700-nm NS with amorphous (A-NS) or amorphous/crystalline (AC-NS) crosslinkers. A single injection of 400 nm NS lowered IOP 24% to 33% for up to 17 days compared to saline, while A-NS and AC-NS lowered IOP 22% to 32% and 18% to 26%, respectively, for up to 32 days ( < 0.046). Over time retinal deposition of Neuro-DiO increased from 19% to 71%; Neuro-DiO released from NS was internalized by RGCs.
A single injection of NS can effectively deliver ocular hypotensive drugs in a linear and continuous manner for up to 32 days. Also, NS may be effective at targeting RGCs, the neurons that degenerate in glaucoma.
Patient compliance is a major issue in glaucoma. The use of NS to deliver a controlled, sustained release of therapeutics could drastically reduce the number of patients that progress to vision loss in this disease.
我们研究了一种缓释药物递送系统——纳米海绵（NS）包裹的化合物经玻璃体内给药降低小鼠眼压（IOP）的效果。
通过向前房注射微珠在小鼠中诱导双侧高眼压。高血压小鼠通过玻璃体内注射接受负载降眼压药物的NS，并监测眼压。使用共聚焦显微镜在玻璃体内注射神经二氢吲哚菁绿（Neuro-DiO）-NS后检查Neuro-DiO的视网膜沉积和视网膜神经节细胞（RGC）摄取情况。
与注射生理盐水相比，负载溴莫尼定的NS可使眼压降低12%至30%，持续长达6天（<0.02），而曲伏前列素-NS可使眼压降低19%至29%，持续长达4天（<0.02）。测试了三种比马前列素NS：一种400纳米的NS和两种700纳米的NS，分别带有无定形（A-NS）或无定形/结晶（AC-NS）交联剂。与生理盐水相比，单次注射400纳米的NS可使眼压降低24%至33%，持续长达17天，而A-NS和AC-NS分别可使眼压降低22%至32%和18%至26%，持续长达32天（<0.046）。随着时间的推移，Neuro-DiO的视网膜沉积从19%增加到71%；从NS释放的Neuro-DiO被RGC内化。
单次注射NS可以以线性和连续的方式有效递送降眼压药物长达32天。此外，NS可能对靶向RGC有效，RGC是青光眼患者中退化的神经元。
患者依从性是青光眼的一个主要问题。使用NS来递送可控的、持续释放的治疗药物可以大幅减少在这种疾病中进展为视力丧失的患者数量。
